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Dr. Li Di Prof. Per Artursson Dr. Alex Avdeef Prof. Leslie Z. Benet Prof. J. Brian Houston Dr. Manfred Kansy Edward H. Kerns Prof. Hans Lennernäs Dr. Dennis A. Smith Prof. Kiyohiko Sugano 《ChemMedChem》2020,15(20):1862-1874
Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients. 相似文献
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Hierarchical micro-nanostructured albite-based glass-ceramic for high dielectric strength insulators
V. Fuertes M.J. Cabrera J. Seores D. Muñoz J.F. Fernández E. Enríquez 《Journal of the European Ceramic Society》2018,38(7):2759-2766
A novel glass-ceramic material based on albite type Na-rich feldspar has been synthesized by conventional ceramic process. High crystallinity, >94%?Vol.% is obtained by fast sintering which allows energy saving processing. Albite is the main crystalline phase and tetragonal SiO2 is a secondary phase. Electrical properties were examined by complex impedance, DC measurements, and dielectric breakdown test. Dielectric characterization shows a non-Debye type dielectric behavior with low dielectric constant, 4.6 at 1?MHz, low dielectric losses, (~10?3 at 1?MHz, and a large dielectric strength, ~60?kV/mm), that it is the largest value reported in ceramic insulators. Those dielectric properties are attained by the low glassy phase content in the samples and their unique micro-nanostructure. All these properties make this novel material a very promising candidate in the market of ceramic electrical insulator, highlighting for high-voltage applications. 相似文献
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Based on the phase transformation theories, especially the T0 concept of bainite transformation, alloy optimisation of bainitic steel with carbides has been carried out aiming at the produce of plastic mould with large cross-section. The effect of manganese and silicon on proeutectoid ferrite and bainite transformation is explored by dilatometric analysis, XRD and different microscopy techniques. The results show that after the alloy optimisation, the transformation of proeutectoid ferrite is suppressed and when the cooling rate is lower than 0·1°C?s??1, the new lower bainite transformation appears by decreasing carbon capacity of austenite and promoting carbide precipitation. Industrial production proves that the optimised alloy SDP1 can meet the demand for the plastic mould with the thickness of 1050?mm. 相似文献
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